With the capability of precisely locating chemical compositions, elastic properties, and interfaces in a material, additive manufacturing provides new avenues to designing tough materials by controlling the crack path, which is predominately influenced by meso-scale material features. Here, we explore the problem of mesostructure toughening, that is, to optimize the fracture toughness for a given loading condition through meso-scale materials design in additive manufacturing. From compact tension test, we show that the fracture toughness of meso-structured nylon and fiber-reinforced composites is significantly improved as compared to their monolithic counterparts. By introducing interfaces as crack arrestors, the crack tip is blunted and the driving force for crack propagation is decreased; by forming Bouligand structures as crack dividers, the crack path is deviated from a direct route and the energy cost for crack propagation is significantly increased. Implementation of mesostructure design in metallic materials will also be discussed for toughness optimization.